Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Temperament and Impulsivity Predictors of Smoking Cessation Outcomes

Aims: Temperament and impulsivity are powerful predictors of addiction treatment outcomes. However, a comprehensive assessment of these features has not been examined in relation to smoking cessation outcomes.Methods: Naturalistic prospective study. Treatment-seeking smokers (n = 140) were recruited as they engaged in an occupational health clinic providing smoking cessation treatment between 2009 and 2013. Participants were assessed at baseline with measures of temperament (Temperament and Character Inventory), trait impulsivity (Barratt Impulsivity Scale), and cognitive impulsivity (Go/No Go, Delay Discounting and Iowa Gambling Task). The outcome measure was treatment status, coded as “dropout” versus “relapse” versus “abstinence” at 3, 6, and 12 months endpoints. Participants were telephonically contacted and reminded of follow-up face to face assessments at each endpoint. The participants that failed to answer the phone calls or self-reported discontinuation of treatment and failed to attend the upcoming follow-up session were coded as dropouts. The participants that self-reported continuing treatment, and successfully attended the upcoming follow-up session were coded as either “relapse” or “abstinence”, based on the results of smoking behavior self-reports cross-validated with co-oximetry hemoglobin levels. Multinomial regression models were conducted to test whether temperament and impulsivity measures predicted dropout and relapse relative to abstinence outcomes.Results: Higher scores on temperament dimensions of novelty seeking and reward dependence predicted poorer retention across endpoints, whereas only higher scores on persistence predicted greater relapse. Higher scores on the trait dimension of non-planning impulsivity but not performance on cognitive impulsivity predicted poorer retention. Higher non-planning impulsivity and poorer performance in the Iowa Gambling Task predicted greater relapse at 3 and 6 months and 6 months respectively.Conclusion: Temperament measures, and specifically novelty seeking and reward dependence, predict smoking cessation treatment retention, whereas persistence, non-planning impulsivity and poor decision-making predict smoking relapse.This research was funded by the Occupational Medicine Area (Prevention Service); Department of Personality, Assessment and Psychological Treatment, University of Granada (Spain); and Ministerio de Economía y Competitividad grant (MINICO, ref. # PSI2013-45055-P) for the first and second authors

Nicotine withdrawal alters neural responses to psychosocial stress

Psychosocial stress is considered to be an important mechanism underlying smoking behavior and relapse. Thus, understanding the effects of acute nicotine withdrawal on responses to stress is important to intervene to prevent stress-induced relapse. The current study investigated the neural correlates of psychosocial stress during acute nicotine withdrawal in chronic smokers. Thirty nine treatment-seeking smokers were randomized to one of two conditions (abstinent 24 hours (n=21) or smoking as usual (n=18)). They were then exposed to the Montreal Imaging Stress Task (MIST), a psychosocial stress task consisting of difficult mental arithmetic problems while receiving negative performance feedback while undergoing functional magnetic resonance imaging (fMRI). Subjective measures of stress increased following the MIST, compared to baseline. Whole brain between-group analysis identified significant activation clusters in four regions for the stress induction minus control contrast: inferior frontal gyrus (IFG), anterior/para cingulate cortex (ACC), precuneus, and supramarginal gyrus (SMG). In all regions, the deprived group showed significantly greater activation compared to the non-deprived group. No significant correlations were found between subjective stress and BOLD signal activation (ps>0.07). This study provides new evidence that brain regions previously shown to be predictive of relapse, such as the precuneus and IFG, display heightened neural responses to stress during nicotine deprivation. These data identify the brain regions that may be associated with withdrawal-related stress responses. Increased stress-related activation during nicotine withdrawal may identify those most vulnerable to relapse and represent a target for novel pharmacological intervention